miR-154上调Wnt/β-catenin信号通路在肺纤维化中的作用及机制研究

项目名称： miR-154上调Wnt/β-catenin信号通路在肺纤维化中的作用及机制研究

项目编号： No.81460013

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 曾林祥

作者单位： 南昌大学

项目金额： 50万元

中文摘要： 肌成纤维细胞生成是肺纤维化形成的重要一环，研究证实：miR-154可增强肺成纤维细胞的增殖和迁移能力，抑制Wnt信号通路后miR-154作用受到逆转。我们的前期研究及文献证实：Wnt信号通路和miR-154在肺纤维化组织中表达上调。生物信息学分析提示：miR-154参与调控Wnt/β-catenin通路。据此提出假设：miR-154上调Wnt信号通路在肺纤维化中起重要作用。本研究拟TGF-β1、miR-154等处理肺成纤维细胞，研究Wnt信号通路变化情况，验证miR-154对靶基因Dkk2的调控作用；用ICG-001抑制Wnt通路，研究其对miR-154作用的影响；并研究miR-154对小鼠肺纤维化的作用。从细胞水平阐述miR-154上调Wnt信号通路调控肺纤维化的机制，从动物水平验证miR-154在肺纤维化中的作用。该研究结果将进一步揭示肺纤维化的发病机制，为肺纤维化的治疗提供新靶点。

中文关键词： 肺纤维化；miR-154；Wnt/β-catenin信号通路

英文摘要： Myofibroblast formation is the important step in the lung fibrosis development. Studies show miR-154 increase migration and proliferation of lung fibroblasts, the increase in proliferation induced by TGF-β1 was not observed when normal human lung fibroblasts or IPF fibroblasts were transfected with a miR-154 inhibitor. inhibitors of the Wnt/β-catenin pathway, reduced the proliferative effect of miR-154.Our first stage study and documents proved activation and upregulation of Wnt/β-catenin signal pathway and miR-154 in lung fibrosis tissue.The online biological information study analysis indicated that miR-154 participate in the regulation of Wnt/β-catenin signal pathway. According the information,we conclude that the role of upregulation of the Wnt/β-catenin pathway by miR-154 is very important in lung fibrosis.In this study, We will treat the lung fibroblasts with TGF-β1 and miR-154 agomirs or mir-154 antagomirs, study the change of Wnt/ β-catenin signal pathway. Then use ICG-001 to inhibit Wnt/β-catenin signal pathway, analyze the effection; We will also use bleomycin to induce mice lung fibrosis, study the role of miR-154 in lung fibrosis. To elaborate the mechanism of miR-154 upregulating Wnt/β-catenin pathway in lung fibrosis on cellular level; then test and verify the role of miR-154 in mice pulmonary fibrosis. The study will futher reveal the molecular mechanism of lung fibrosis, and explore new target spot during the treatment of lung fibrosis.

英文关键词： lung fibrosis;miR-154;Wnt/β-catenin signal pathway